Non-Hodgkin’s Lymphoma

5th ASH Refresher Course

Tanin Intragumtornchai, M.D.

Special Problems in B-Cell Lymphomas

• Burkitt lymphoma in adults

Perkins AS, Friedberg JW, Rochestor U, NY
• Primary mediastinal B-cell lymphoma
Johnson PWM, Davies AJ, U Southampton, UK
• Marginal zone lymphomas
Kahl B, Yang D, U Wisconsin
Burkitt Lymphoma: Diagnostic Features

• High rate of proliferation (Ki-67 > 95%)

• Activation of MYC gene at 8q24 (Giemsa
banding or FISH)
• Relative simplicity of karyotype
• No cleaves or folds in nuclear contour
• Lack of Tdt positivity
 Key Clinical Features
• Bulky abdominal mass, B symptoms,
laboratory evidence of tumor lysis
• 70% bone marrow involvement
• 40% leptomeningeal involvement
 Treatment
• Intensive, short duration chemotherapy
(high-dose alkylating agents, CNS
prophylaxis)
• ALL-like regimen
• Therapy included consolidation with auto-
SCT
 OS According to Age
All cases > 40 yrs
• CODOX-M/IVAC 71% 39%

• ALL-like 51% 40%

• Hyper-CVAD 57% 17% (> 60 yrs)

89% (rituximab-
based)
 Conclusion
• A highly curable malignancy
• Inferior outcome in patients age > 40
years
• Important to differentiate from “atypical
Burkitt”
Primary Mediastinal B-Cell Lymphoma

• Median age 37 years

• Stage I/II 74%
• Elevated LDH 77%
• Bulk (>10 cm) 75%
• Pleural or pericardial 50%
effusion
 Treatment
• Role of third generation regimen
• Role of rituximab
• Consolidating radiotherapy
• How to evaluate residual mass?
• Role of HDT
 Role of Third Generation Regimen

• Three large retrospective (one population-

based) studies showed superior OS for
MACOP-B, VACOP-B compared to CHOP
(70% vs 50%, p < 0.05)
 Role of Rituximab

• Addition of rituximab to dose-adjusted

EPOCH (n = 44) was associated with
favorable EFS and OS (87% and 93%, p <
0.05)
• Retrospective population-based study did
not showed superiority of R-CHOP over 3rd
generation regimen
 Consolidating Radiotherapy

• Mediastinal radiotherapy is essential in

patients achieving PR after initial
chemotherapy (increased CR rate from
42% to 95%)
• Role in patients with CR is questionable in
particular those treated with rituximab-
based regimen
 How to Evaluate Residual Mass?

• FDG-PET is the tool of choice

• All patients with positive PET relapsed
compared to 26% in patients with negative
PET
• Gallium scan is less expensive but time-
consuming and low spatial resolution
 Role of HDT

• No role in patients with first CR

• In chemosensitive relapse and refractory
disease, the long-term OS were 40-70%
and 50-60%, respectively
 Nodal MZL
• Median age 60 years
• Male : female 1:1
• Present in advanced stage with non-bulky
widespread lymphadenopathy
• 1/3 had bone marrow involvement
 Nodal MZL
• Clinical course resembled other nodal
indolent lymphomas
• Prognosis less favourable compared to
MALT, splenic MZL and FL. Roughly
comparable to SLL.
• 16% transformed to large-cell in 4.5 years
• Apply same treatment approach as FL
 Splenic MZL
• Present with moderate to massive
splenomegaly
• Cytopenias due to splenic sequestration
(main factor) and marrow involvement
• Best diagnostic tool is bone marrow
examination
• Differentiate with HCL by showing
negative staining to CD25 and CD103
 Splenic MZL
• Splenectomy is the treatment of choice
• In asymptomatic patients using watch and
wait policy, median time to treatment is 3
years
• Systemic chemotherapy (favored purine
analogues) is indicated in patients
contraindication to splenectomy or had
heavy burden of disease outside spleen
 Splenic MZL
• 5-year OS 76%
• Three adverse poor prognostic factors:
hemoglobin < 12 g/dl, serum albumin <
3.5 g/dl and LDH > ULN
 Gastric MALT Lymphomas
• Comprised 30% of all MALT lymphomas
• Endoscopy showed erythema, erosions,
ulceration. Masses are uncommon.
• Establish H. pylori status is essential (histologic
examination, biopsy urease test, urea breath
test, stool antigen test and selorogy).
• 90% of patients had H. pylori infection
• t(11;18) evaluation by FISH
 Treatment
• 75% of stage IE patients with H. pylori infection
and without t(11;18) will respond to H. pylori
eradication
• Response is quite slow. Complete response is
established in one year.
• Repeat endoscopy every 3-6 months until
normalization of gastric mucosa then annually
• Routine biopsy of normal appearing mucosa is
not recommended
 Treatment
• Low-dose radiotherapy is indicated in
patients with H-pylori negative or failure to
H. pylori eradication (100% OS)
• Patients with advanced disease were
treated with the same principle as patients
with advanced stage FL
 Non-gastric MALT Lymphomas

• Comprised 70% of all MALT lymphomas

• Association with infectious agents
- B burgdorfi: cutaneous MALT lymphoma
- C psittaci: conjunctival MALT lymphoma
- C jejuni: IPSID
• Frequency of associations and role of
antimicrobial therapy are still under
investigations
 Treatment
• Low-dose radiotherapy is the treatment of
choice
• 5-year OS > 90% and 10-year OS > 80%
 Peripheral T-Cell Lymphomas
• Prognosis and 1ry therapy in PTCL
Kerry J Savage (BC Cancer Agency)
Addition of Etoposide to CHOP/CHOP-
Like Regimen
• CHOEP vs CHOP : EFS 71% vs 50% (p
=.01)(GNHLG)
• VIP/ABVD vs CHOP : no difference in OS
and EFS (GOELAMS)
 Subtype-Specific Therapies
• Cutaneous ALCL: local excision with or
without radiotherapy
• ALK pos ALCL : CHOP
• Localized NK/T lymphoma, nasal type:
- primary radiotherapy is the principal
treatment. Chemotherapy provide additional
benefit?
- Initial RT vs initial CT : CR 83% vs 20% (Li et
al, JCO 2006)
 Conclusions
• Outcome is unsatisfactory with CHOP
• Therapies should be tailored according to
the subtypes
• Large well-designed RCTs coorporating
novel therapies are urgently needed.
 WHO 2008
B-Cell Lymphomas (New Addition)
• Primary cutaneous follicle center cell lymphoma
• DLBCL, NOS
- T-cell/histiocyte rich large B-cell lymphoma
- Primary DLBCL of CNS
- Primary cutaneous DLBCL, leg type
• DLBCL of chronic inflammation
• ALK-pos large B-cell lymphoma
• Plasmablastic lymphoma
• Large B-cell lymphoma associated with Castleman disease
• B-cell lymphoma, intermediate beteween DLBCL and BL
• B-cell lymphoma, intermediate beteween DLBCL and HL
 WHO 2008
T-Cell Lymphomas (New Addition)
• Systemic EBV positive-T-cell lymphoproliferative
diseases of childhood
• Hydroa vacciniiforme-like lymphoma
• Primary cutaneous CD30 positive T-cell
lymphoproliferative disorders
- lymphomatoid papulosis
- primary cutaneous ALCL
• Primary cutaneous gamma-delta T-cell lymphoma
• ALCL, ALK pos
 DLBCL of Chronic Inflammation

• Long standing chronic inflammation

• Associated with EBV infection
• Involve narrow space, body cavities
• Prototype : pyothorax-ass-lymphoma.
• Poor pg, 5-yr OS 25-30%
Hydroa Vacciniiforme-Like Lymphoma

• Children/adolescence of Asian, Native

Americans, South Americans
• Associated with EBV
• Associated with insect bites, sun
sensitivity
 Lymphomatoid Papulosis

• Chronic relapsing papular, papulonecrotic

and/or nodular skin lesions.
• Good prognosis